Background: Ulcerative colitis (UC) is an idiopathic and heterogeneous large intestine disease, characterized by chronic mucosa and submucosa inflammation. Alteration of the intestinal microbiome in UC may be responsible for modifications in metabolite production. Aim: To investigate the microbiota status and trimethylamine-N-oxide (TMAO) metabolite levels in patients with UC according to clinical and endoscopic activity. Methods: As part of a grant project AP14871959 from September 2022 to October 2023, 31 patients with UC and 15 healthy volunteers over 18 years at the Clinic of NCJSC “KMU” were assessed for blood TMAO level and metagenomic sequencing of fecal microbiome. Results: A significant depletion of the main representatives of Bacteroides, Parabacteroides, Prevotella; and an increase in the relative abundance of the genera Actinomyces, Klebsiella, Limosilactobacillus, Streptococcus, Escherichia-Shigella were detected in patients with UC. The number of p_Actinobacteria (g_Collinsella) and p_Eubacterium (g_Xylanophilum) representatives with genes encoding TMA-trimethylamine conversion is significantly reduced in UC patients. TMAO levels were significantly lower in UC patients than in healthy individuals (0.233 µmol/L, p = 0.004). TMAO decreased with disease severity and significantly differed between patients with different activities (p = 0.034). Conclusions: The composition of the intestinal microbiome changes and the level of TMAO decreases in patients with UC at different activities.

(1) Background: Endothelial dysfunction is a key mechanism in the pathogenesis of COVID-19. High endothelin-1 during COVID-19 is associated with severe complications and increased mortality rates during hospitalization. This study is aimed to investigate the association of endothelin-1 levels with the risk of 30-day and 12-month all-cause mortality in patients with prior COVID-19. (2) Methods: A prospective study was conducted involving patients with COVID-19 in Karaganda, Kazakhstan. The level of endothelin-1 in the blood serum was evaluated by ELISA. Univariate and multivariate Cox regression was used to determine factors and significance of endothelin-1 associated with the risk of mortality within 30 and 365 days from hospitalization. (3) Results: The median endothelin-1 was higher in the group of patients who passed away within 30 days. The group showed statistically significant differences when compared to healthy volunteers from the control group (p = 0.0001), surviving patients (p = 0.001), and those who passed away within a year (p = 0.002). (4) Conclusions: Endothelin-1 levels are associated with increased mortality risk during the acute period of COVID-19, while plasma endothelin-1 level association with COVID-19 survivor mortality risk does not persist after 12 months.

Background/Objectives: This study aims to investigate the potential etiopathogenesis of HFpEF development and identify possible different phenotypes of HFpEF in patients with chronic obstructive pulmonary disease (COPD) and systemic sclerosis-associated interstitial lung diseases (SS-ILDs). It could help clinicians improve early HFpEF personalized detection and management. Methods: This study included 150 patients with chronic lung diseases (CLDs), such as COPD and SS-ILD, who were outside of exacerbation, had no history of chronic heart failure (CHF), and had a left ventricular ejection fraction (LV EF) of ≥50%. The functional status of the lungs, heart, endothelial dysfunction, and acid–base balance was assessed. The results obtained were compared in groups of patients with CLD depending on the presence or absence of HF with preserved ejection fraction (HFpEF). The diagnosis of HFpEF was established based on the HFA-PEFF Score classification. Nonparametric statistical methods were used. Results: In patients with CLD, indicators such as age, longitudinal size of the right atrium, mid-regional pro-atrial natriuretic peptide (MR-proANP), and highly sensitive cardiac troponin T (hsTnT) were higher than in the group of patients without HFpEF. In patients with COPD and HFpEF, statistically significant changes were found in the volume of the left atrium. In patients with SS-ILD and HFpEF, statistically significant differenceswere found in SBP before and after the 6 min walk test (6MWT), the Borg scale before 6MWT, MR-proANP, and the longitudinal dimension of the right atrium. Conclusions: The results of our study allow us to identify two different mechanisms of HFpEF development: In patients with COPD, the predominant factor in the development of HFpEF was hypoxia, while in patients with SS-ILD, myocardial dysfunction with remodeling developed against the background of secondary pulmonary hypertension, highlighting the importance of phenotype-specific evaluation. These findings suggest potential approaches for personalized risk stratification and the development of targeted management strategies for patients with HFpEF.

Background and Objectives: Chronic lung diseases act as multi-organ conditions in which systemic inflammation, vascular dysfunction, and fibrosis intersect. The pulmo-renal continuum—functional crosstalk between lungs and kidneys—remains poorly characterized. We compared year-long changes in endothelin-1 (ET-1), galectin-3 (Gal-3), renal indices (eGFR, ACR), and quantitative CT densitometry in COPD and systemic sclerosis-associated ILD (SSc-ILD). Materials and Methods: In this prospective observational study (January 2023–December 2024), 112 patients were consecutively enrolled (COPD, n = 58; SSc-ILD, n = 54). Assessments were performed at baseline and 12 months. ET-1 (ELISA) and Gal-3 (chemiluminescence) were measured in serum; eGFR was calculated by the creatinine-based CKD-EPI (2021) equation; ACR was photometric. High-resolution chest CT provided lung volume and parenchymal density (Hounsfield units) at six predefined axial levels per lung. Non-parametric statistics were applied: Wilcoxon signed-rank (within-group), Mann–Whitney U (between-group), and Spearman rank correlations for associations; results are reported with p-values (and 95% CIs). Results: Baseline eGFR was normal (COPD 90.37; SSc-ILD 92.4 mL/min/1.73 m²). eGFR declined by 6.76% in COPD (p = 0.001) and 3.16% in SSc-ILD (p = 0.029). ET-1 increased in both cohorts but more in COPD (+83.78%, p = 0.0002) than in SSc-ILD (+23.83%, p = 0.0001). Gal-3 rose significantly only in SSc-ILD (+10.2%, p = 0.043). FVC decreased in COPD (−4.01%, p = 0.01) and was unchanged in SSc-ILD. Total lung volume declined in SSc-ILD (−6.08%, p = 0.02) but not in COPD. CT density shifts were small: several slices in COPD and one slice (L6) in SSc-ILD reached statistical but not biological relevance. Conclusions: COPD exhibited larger vascular and renal biomarker shifts (ET-1 up, eGFR down, ACR up), suggesting systemic inflammation and early renal involvement. In SSc-ILD, biomarker and CT changes predominantly reflected pulmonary fibrosis progression with limited renal impact. Integrating biomarkers with quantitative CT may help delineate organ-specific trajectories along the pulmo-renal continuum; longer, larger studies are warranted. Limitations: This was a single-center cohort with a modest sample (58 COPD and 54 SSc-ILD) and a 12-month, two-time-point follow-up, which may not capture long-term trajectories and may limit it generalizability; larger multicenter studies with an extended follow-up are warranted.

Биоимпедансометрия у пациентов с хроническими заболеваниями легких в контексте пульмокардиоренального континуума

Background/Objectives: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) and chronic obstructive pulmonary disease (COPD) are linked to multi-organ vulnerability involving the lungs, heart, and kidneys. This study aimed to compare the annual changes in pulmonary, cardiac, and renal parameters in patients with SSc-ILD and COPD across three consecutive years, using both individual biomarkers and integrated composite profiles. Methods: This observational longitudinal study included repeated assessments in 2023, 2024, and 2025. Functional, laboratory, and imaging parameters were collected: 6-min walk test (6MWT), SpO₂ (pre-/post-exercise), spirometry/CT lung volumes, gas exchange (pO₂/pCO₂/lactate), echocardiography [left ventricular ejection fraction (LVEF), estimated systolic pulmonary artery pressure (sPAP)], cardiac biomarkers (NT-proBNP, MR-proANP, hsTnT), renal markers [eGFR, creatinine, albuminuria, albumin-to-creatinine ratio (ACR)], heart rate variability (HRV), and renal CT densitometry. All markers were standardized (z-scores, higher values = worse). Subprofiles were generated and aggregated into three integrated profiles (cardiac, renal, pulmonary). Within-group dynamics were analyzed using the Wilcoxon signed-rank test (year-to-year deltas), between-group comparisons with the Mann–Whitney U test, effect sizes via Cliff’s delta, and multiple testing correction with the Benjamini–Hochberg false discovery rate (FDR). Results: Exercise tolerance declined in both groups: by 2025, 6MWT distance decreased by −10 m in SSc-ILD (p = 0.006; q = 0.010) and −20 m in COPD (p = 0.002; q = 0.004); post-exercise SpO₂ fell in both cohorts (both p < 0.001; q < 0.001). MR-proANP remained consistently higher in SSc-ILD across all years (p ≤ 0.005; q ≤ 0.028). sPAP increased in both groups, reaching higher values in COPD by 2025 (p = 0.007; q = 0.033). NT-proBNP and hsTnT increased over time, while eGFR declined, and ACR rose in both cohorts (both p < 0.001; q < 0.001). HRV (HF/total power) decreased by 2025. Composite profiles showed: in 2023, the cardiac profile was worse in SSc-ILD (δ ≈ 0.27; p = 0.011; q = 0.048), but differences diminished by 2025; the renal profile was initially worse in SSc-ILD but later shifted unfavorably in COPD; the pulmonary profile showed no consistent between-group differences. Conclusions: Over three years, patients with SSc-ILD and COPD exhibited concordant deterioration in pulmonary, cardiac, and renal function. Distinct leading markers emerged: desaturation during exercise and neurohormonal activation (MR-proANP) in SSc-ILD, versus reduced 6MWT and higher sPAP in COPD. These findings support the need for integrated monitoring of the cardio–pulmo–renal continuum. Limitations include the observational design, multiple comparisons, and absence of advanced repeated-measures modeling.